Fabio Quartararo won his second consecutive race when he took the Portuguese MotoGP at Portimao on Sunday, with six-time champion Marc Marquez seventh in his first race back after nine months out.
"I feel full confidence," said French Yamaha rider Quartararo, who started last season strongly only to fade out of contention.
Italian Francesco Bagnaia on a Ducati was second with Spanish world champion Joan Mir of Suzuki third.
Franco Morbidelli (Yamaha-SRT) and South African Brad Binder (KTM) completed the top five.
Marquez's seventh-placed finish came on his return after three bouts of surgery on the right arm he broke in the 2020 opener at Jerez.
He qualified on the second row and admitted on Saturday that he was "going to suffer" after such long time away from racing.
Quartararo's compatriot Johann Zarco (Ducati-Pramac), who had led the riders' standings before Sunday's race, crashed out on lap 20 while challenging for the podium after leading in the early stages.